Objective: To gain better understanding of basic mechanisms (cellular and humoral) governing the immune response to tumor specific antigens. Approach: Tumors induced by either chemical carcinogens or RNA- tumor viruses, as well as spontaneous mouse mammary carcinomas, are studied in vivo as well as in vitro. A microcytotoxicity assay is extensively used in the in vitro studies to investigate cell-mediated immune reactions to tumor antigens (the type of effector cells involved etc) and the antagonistic, as well as synergistic, influences of serum factors on such reactions, particularly the ability of antigen-antibody complexes and free tumor antigen circulating in tumor-bearer serum to block (inhibit) cell-mediated destruction of tumor cells in vitro. The molecular nature of the blocking serum factors is being studied. Another aspect of this work concerns the development of animal models for immunological prevention and therapy of tumors with a particular emphasis on tumors having cross-reacting antigens.